Bioeffecting agents--agents which engage in a biological activity or are effective in modulating a biological activity--are often applied to the surface of articles for a variety of purposes. For example, bath mats are often sprayed with agents containing benzylammonium salts to inhibit the growth of microbes. Bioeffecting agents are also used to alter the surface properties of the materials to which they are applied. A pharmaceutical preparation of heparin when applied to a medical device provides its surfaces with antithrombogenic properties.
To prolong the duration of the bioeffecting activity or to delay its initiation, bioeffecting agents have been encapsulated or embedded in materials for subsequent release in particular locations or under particular conditions. For example, polyglycolic and polylactic acids have found significant usage as resorbable biomaterials and have often been blended during processing to include a variety of bioeffecting agents. The bioeffecting agents contained in these materials are released as the products degrade. The rate of delivery of the agents is determined by the local conditions which affect the diffusion of the bioeffecting agents and the degradation of the enclosing materials. Bioeffecting agents have also been incorporated in materials such as hydrogels which swell in moist environments. Hydrogels release the agents through diffusion into the local environment.
Various types of chemical attachments have been employed to bind bioeffecting agents to articles in attempts to improve the duration of the bioeffecting activity. A number of ionic bonds have been used, because bioeffecting agents possessing sufficient ionic charge can be readily attached to the surfaces of articles containing the opposite ionic charge. Hsu, for example, in U.S. Pat. No. 4,871,357, describes an ionic heparin coating for use with medical devices. The release of materials which are attached to substrates with ionic bonds is governed both by the strength and number of the ionic pairs, and by local conditions such as pH and moisture. Ionic bonds disassociate quite rapidly under moist conditions. Even ionic systems of attachment designed to include protectants against wet environments tend to be less durable under those conditions. Ionic attachment can also adversely affect the function of bioaffecting materials during the period of attachment.
Covalent bonds, relying on a number of functional groups, have been used to attach bioeffecting agents to the surface of articles. In U.S. Pat. No. 4,810,784, Larm described a method of covalent attachment using glutaraldehyde and aldehyde conversions, while Burns utilized a method of attachment relying on carbodiimide conversion in U.S. Pat. No. 5,527,893. Guire, in U.S. Pat. No. 5,336,579, described a method which used a combination isocyanate and photo-activation hydrogen abstraction. While these types of bonds provide good attachment of the agent to the article, they can be difficult and complicated to form on the surface of the substrate, often requiring multiple modifications. In addition, the final covalent bond formed is not generally reversible, and the bioaffecting activity of the agent is often altered significantly by its interaction with the functional group providing the attachment.